REGULATION OF THE ESTROGEN-RECEPTOR AND ITS MESSENGER-RIBONUCLEIC-ACID IN THE OVARIECTOMIZED SHEEP MYOMETRIUM AND ENDOMETRIUM - THE ROLE OFESTRADIOL AND PROGESTERONE

Estrogen receptor (ER) mRNA is dramatically increased in sheep myometr ium and endometrium during glucocorticoid-induced premature labor and term spontaneous labor. However, the underlying mechanism for the up-r egulation of uterine ER in labor is still unknown. We used ovariectomi zed (OVX) nonpregnant sheep to analyze the role of estradiol and proge sterone in the regulation of myometrial and endometrial ER protein and ER mRNA in vivo. Twenty-one OVX ewes were treated with saline (n = 6) , or with estradiol infused i.v. for 2 days (50 mu g/day, n = 5), or w ith an intravaginal progesterone sponge for 10 days (containing 0.3 g progesterone, n = 5), or with an intravaginal progesterone sponge for 10 days with estradiol (50 mu g/day) administered on Days 9 and 10 wit h the progesterone sponge still in place (n = 5). The ER protein conce ntration in both cytosolic and nuclear compartments, analyzed by Weste rn blot, increased significantly (p < 0.05) in the myometrium after es tradiol treatment, while progesterone alone had no detectable effect o n ER level. Elevated ER protein was observed only in the nuclear fract ion of endometrium. However, when estradiol was given together with pr ogesterone treatment, progesterone antagonized the up-regulatory effec t of estradiol on the ER level both at the endometrium and myometrium. The changes in cellular ER mRNA followed the pattern observed at the ER protein level. Estrogen receptor mRNA was elevated significantly (p < 0.01) only in estradiol-treated ewes. Expression of the ER gene in ewes receiving progesterone alone or progesterone combined with estrad iol was similar to that of the control group. From these observations we conclude that ER gene expression and active ER synthesis in nonpreg nant sheep myometrium and endometrium are estradiol-dependent, Progest erone antagonizes this estrogen action. Progesterone down-regulated th e elevated ER mRNA when used together with estradiol. In situ hybridiz ation showed that ER mRNA was evenly distributed in the smooth muscle cells and blood vessels of the myometrium and the epithelial cells of the glands in endometrium. In conclusion, we have observed estradiol-d ependent activation of ER gene expression as well as active ER synthes is in the nonpregnant sheep myometrium and endometrium. Progesterone a cted as an antagonist of estradiol on ER gene expression.